School-age outcomes of newborns treated for persistent pulmonary hypertension.

OBJECTIVE: The aim of this study was to describe the school-age outcome of a cohort of children treated with intensive care support for persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: From 187 term newborns treated for PPHN as neonates, 109 were seen at school age (73% of 150 survivors and 58.2% of the original cohort). Of these 109 term newborns, 77 were treated with inhaled nitric oxide (iNO); of which 12 received extracorporeal membrane oxygenation (ECMO). The remaining 32 received conventional management with no exposure to iNO. Patients were seen at school age (mean 7.1 years). A medical history and physical exam were completed, growth was measured, and chest X-ray and echocardiogram were performed. Psychometric assessments included the Wechsler Scales (Preschool or Child), Vineland Adaptive Behavior Scales, Kaufman Test of Educational Achievement, Children's Category Test, Wisconsin Card Sorting Test and Achenbach Child Behavior Checklist. RESULT: Medical, neurodevelopmental and social/emotional/behavioral outcome did not differ between children treated with iNO, with or without ECMO, and those managed with no exposure to iNO. Overall, 24% had respiratory problems, 60% had abnormal chest X-rays and 6.4% had some sensorineural hearing loss. The cohort performed at the average level for full scale IQ, adaptive function, academic achievement, higher-order cognition and executive functioning, and social/behavioral/emotional functioning. Overall, 9.2% of the cohort had a full scale IQ less than 70 and 7.4% had an IQ from 70 to 84. CONCLUSION: The outcome for this cohort of children treated as newborns for PPHN, which included a large group of infants exposed to iNO, was comparable to previous reports of children treated with ECMO or conventionally.

Echocardiographic outcome of infants treated as newborns with inhaled nitric oxide for severe hypoxemic respiratory failure.

OBJECTIVE: To determine the cardiovascular outcome of a group of term newborns treated with inhaled nitric oxide (iNO) for severe hypoxemic respiratory failure with associated persistent pulmonary hypertension. STUDY DESIGN: We performed echocardiographic evaluations in 40 survivors treated for severe neonatal hypoxemic respiratory failure. Each of the 40 had at least 2 follow-up echocardiograms at 3 or 6 and 24 months. These studies were compared with echocardiograms done in infants in a normal, age-matched control group. RESULTS: Three of 31 infants met echocardiographic criteria for pulmonary hypertension at the 3-month examination. Two of the 3 had associated structural heart disease (1 with an atrial septal defect and 1 with a ventricular septal defect). At 24 months only 1 patient had pulmonary hypertension. This infant had an atrial septal defect that was surgically closed shortly after the 24-month echocardiogram because of the pulmonary hypertension. Group comparisons of 3- and 24-month echocardiographic variables showed no differences between the study and control groups. In the 31 infants in whom serial studies were completed, expected age-related changes were demonstrated between the 3- and 24-month examinations. CONCLUSIONS: The incidence of residual pulmonary hypertension in infants treated as newborns for severe hypoxemic respiratory failure is low. The group at highest risk is those with structural heart disease.

Survivors of neonatal extracorporeal membrane oxygenation at school age: unusual findings on intelligence testing.

Data are presented on 17 children who received extracorporeal membrane oxygenation (ECMO) in the neonatal period for persistent pulmonary hypertension (PPHN). These children are being followed as part of a larger program of follow-up research on children who have been treated for PPHN with several treatment methods. On intelligence testing at ages 5 to 8 years, these 17 children had unusual patterns of results. A higher-than-predicted percentage of the ECMO survivors had discrepancies between their Verbal and Performance IQ and a much-higher-than-predicted percentage had areas of unusual strength or weakness on their IQ subtest scores. Also, there was a significant correlation between the amount of time a child received ECMO and the child's Performance IQ: the longer the child received ECMO, the higher the Performance IQ. While findings of unusual weaknesses or deficits on intelligence testing at school age in children who have been severely ill in the neonatal period are not unusual, findings of high scores and areas of strength are not easily explained, particularly when these findings seem to relate to an invasive treatment like ECMO. Similar findings have been reported in two other small studies, which suggest that the impact of ECMO on the developing infant brain may not be purely detrimental.

Longitudinal follow-up of a cohort of newborn infants treated with inhaled nitric oxide for persistent pulmonary hypertension.

OBJECTIVE: To describe the outcome of a group of term newborn infants treated with inhaled nitric oxide for severe persistent pulmonary hypertension. STUDY DESIGN: We performed a prospective longitudinal medical and neurodevelopmental follow-up of 51 infants treated as neonates for persistent pulmonary hypertension of the newborn with inhaled nitric oxide. The original number of treated infants was 87, of whom 25 died in the neonatal period; of 62 infants who survived, 51 were seen at 1 year of age and 33 completed a 2-year evaluation. Statistical analysis used population medians, means, and standard deviations for parameters assessed. Paired t tests and chi-square analysis were used to compare outcomes measured at 1 year with assessment at 2 years for the 32 infants seen at both 1- and 2-year visits. RESULTS: At 1-year follow-up median growth percentiles were 20%, 72.5%, and 50% for weight, length, and occipitofrontal circumference, respectively. Thirteen of 51 infants (25.5%) were < 5th percentile in weight. Nine of 51 infants (17.6%) had feeding problems (need for gastrostomy feeding or gastroesophageal reflux), and 14 (27.5%) had a clinical diagnosis of reactive airways disease. Infant development as measured by the Bayley Scales of Infant Development was 104 +/- 16 for the mental development index and 97 +/- 20 for the psychomotor index. Six of 51 infants (11.8%) were found to have severe neurologic handicaps, defined as a Bayley score on either the mental development or psychomotor index of < 68, abnormal findings on neurologic examination, or both. Fewer children (6.1% vs 15.7%) required supplemental oxygen at 2 years compared with 1 year, and performance on the psychomotor index of the Bayley Scales improved significantly. CONCLUSIONS: One- and 2-year follow-up of a cohort of infants with persistent pulmonary hypertension of the newborn who were treated with inhaled nitric oxide had an 11.8% (1 year) and 12.1% (2-year) rate of severe neurodevelopmental disability. There are ongoing medical problems in these infants including reactive airways disease and slow growth that merit continued close longitudinal follow-up.